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The skin has very important vital functions for keeping the physiological and biochemical conditions of the body in its optimum state. The most important functions of the skin are: 

  1. Regulates body temperature.

  2. Prevents loss of essential body fluids, and penetration of toxic substances.

  3. Protection of the body from harmful effects of the sun and radiation.

  4. Excretes toxic substances with sweat.

  5. Mechanical support.

  6. Immunological function mediated by Langerhans cells.

  7. Sensory organ for touch, heat, cold, socio-sexual and emotional sensations.

  8. Vitamin D synthesis from its precursors under the effect of sunlight and introversion of steroids.

The epidermis is the outer most layer of skin that acts as a barrier preventing toxic chemical and other materials from penetrating deeper into the skin. This is relatively porous and undergoes changes in thickness in response to different factors such as trauma or pressure.

The layers of the epidermis differentiate and gradually develop to a more rigid structure, which provides a barrier to excessive loss of body fluids and the penetration of noxious substances. The basal layer is the precursor of the different cells of the epidermis which divide, pushed further upwards, loosing much of their metabolic function and enzymatic activity. The spinous layer is characterized by growth of keratin fibrils where these are present also in the cells of the basal layer.

Epidermal cells as they are pushed up away from the basal layer, begin to dehydrate and become filled with cross-linked keratin, which gives the cells a granular appearance. Lamellar bodies containing structured lipids play an important role in skin protection. The intercellular lipids, the corneocytes, amino acids, and other salts from sweat, sebaceous secretions, degradation products from corneal proteins besides lipids and others all have an important barrier effect preventing loss of water and keep the skin pH in its optimum condition (5.5).

The stratum corneum provides most of the barrier function.

The skin acts as a two-way barrier to prevent the inward or outward passage of water and electrolytes. The epidermis largely represents the barrier; whereas once the epidermis is removed the residual dermis is almost completely permeable.

There are two possible routes for the passage of drugs through the epidermis, through the transcellular, which is probably the major pathway for polar substances, and through the intercellular.


The penetration of substances through the skin surface depends upon different factors:

Fig. 8. Stratum corneum with 
the intercellular lipid layers

  1. Age - penetration is more in newborn and children than in adults.

  2. Skin condition - penetration is more on injured or abraded skin surfaces. Chemicals may cause injury and increase penetration.

  3. Hydration of the skin - penetration is more in hydrated skin than dry skin. Hydration increases the permeability of the stratum corneum. Water is an effective penetration enhancer.

  4. Fat content of the epidermis has no much effect on penetration.

  5. Type of vehicles: vehicles may increase penetration and absorption of the drug from the skin surface. This depends on the type of vehicle and the condition of the skin. Certain vehicles that may cause injury to the skin even minimal injury predispose to more penetration of the drugs or other materials applied topically to the skin surface.

  6. Hyperemia - vasodilatation of the blood vessels in response to different stimuli either local or generalized increases the penetration.

  7. Physiological and pharmacological factors

    The penetration in vivo of topically applied substances can be assessed by physiological or pharmacological signs or analyzed by chemical or histological techniques:

  • Vasoconstriction has been utilized for corticosteroids.

  • Vasodilatation for nicotinates.

  • Whealing for histamines.

  • Sweating for pilocarpine.

  • Anesthesia for local anesthetics.

  1. Lipoid soluble substances facilitate penetration of substances applied to the skin surface. Steroid hormones and vitamin D, salts such as chloride and sulfate can penetrate the skin surface. Gases and volatile substances can pass through the skin.


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